The inflamed axis: The interaction between stress, hormones, and the expression of inflammatory-related genes within key structures comprising the hypothalamic-pituitary-adrenal axis
The inflamed axis: The interaction between stress, hormones, and the expression of inflammatory-related genes within key structures comprising the hypothalamic-pituitary-adrenal axis
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DOI：
10.1016/j.physbeh.2013.10.035
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发表时间：
2014-01-30
影响因子：
2.9
通讯作者：
Deak, Terrence
中科院分区：
文献类型：
--
作者：
Hueston, Cara M.;Deak, Terrence
急性应激可增加中枢神经系统、血浆和内分泌腺中细胞因子和其他炎症相关因子的表达，下丘脑-垂体-肾上腺（HPA）轴炎症信号通路的激活可能在后期应激致敏中起关键作用。除了总结应激对中枢神经系统内神经免疫变化的影响外，我们还提出了一系列实验，以表征应激对包括HPA轴（PVN，垂体和肾上腺）在内的关键结构中的白介素- β (IL-1)超家族成员和其他炎症相关基因的影响。随后进行了一系列实验，研究外源性激素（CRH和ACTH）和地塞米松对成年雄性Sprague-Dawley大鼠炎症相关基因表达的影响。结果显示，IL-1和IL-1R2在PVN中具有稳健的、时间依赖的和异步的表达模式，其中IL-6和COX-2在肾上腺中的显著增加是主要发现。外源性CRH和ACTH的影响主要在肾上腺中分离。最后，地塞米松预处理严重减弱了肾上腺的神经免疫变化，但对PVN没有影响。这些发现为应激、HPA轴关键结构中炎症信号因子的表达及其与HPA激素的相互作用之间的关系提供了新的见解，并为更好地理解细胞因子作为下丘脑、垂体和肾上腺敏感性调节剂的作用奠定了基础。(C) 2013爱思唯尔公司版权所有。
Acute stress increases the expression of cytokines and other inflammatory-related factors in the CNS, plasma, and endocrine glands, and activation of inflammatory signaling pathways within the hypothalamic-pituitary-adrenal (HPA) axis may play a key role in later stress sensitization. In addition to providing a summary of stress effects on neuroimmune changes within the CNS, we present a series of experiments that characterize stress effects on members of the interleukin-beta (IL-1) super-family and other inflammatory-related genes in key structures comprising the HPA axis (PVN, pituitary and adrenal glands), followed by a series of experiments examining the impact of exogenous hormone administration (CRH and ACTH) and dexamethasone on the expression of inflammatory-related genes in adult male Sprague-Dawley rats. The results demonstrated robust, time-dependent, and asynchronous expression patterns for IL-1 and IL-1R2 in the PVN, with substantial increases in IL-6 and COX-2 in the adrenal glands emerging as key findings. The effects of exogenous CRH and ACTH were predominantly isolated within the adrenals. Finally, pretreatment with dexamethasone severely blunted neuroimmune changes in the adrenal glands, but not in the PVN. These findings provide novel insight into the relationship between stress, the expression of inflammatory signaling factors within key structures comprising the HPA axis, and their interaction with HPA hormones, and provide a foundation for better understanding the role of cytokines as modulators of hypothalamic, pituitary and adrenal sensitivity. (C) 2013 Elsevier Inc. All rights reserved.